It has become apparent that conditioning of drug effects to cues associated with cocaine and other psychomotor stimulants play a very critical role in the development and maintenance of drug-induced sensitization as well as the addictive process related to these pharmacological agents. Over the past several years we have made considerable progress in elucidating the neurobiological processes involved in the conditioned effects of cocaine. The purpose of these studies was to define further the neuropharmacological and neuroanatomical substrates underlying these conditioned effects and to characterize the behavioral variables involved in their acquisition, retention, and extinction. We have found that environmental stimuli associated with cocaine develop the ability, through classical conditioning, to elicit increases in plasma corticosterone when presented alone. Such conditioned effects were not dependent upon intact 5HT functions. We also found that pretreatment of rats with eticlopride (a D2 DA antagonist) prior to a series of extinction sessions prevented the expression of cocaine-conditioned behaviors but had no effect on the extinction process. Neither the D1 antagonist SCH 23390 nor apomorphine had an appreciable effect on the extinction process. Pretreatment of rats systemically with MK-801 (a glutamate antagonist) or N-nitro-L- arginine methyl ester (L-NAMF), a nitric oxide synthase inhibitor, prevented the acquisition of cocaine-induced conditioned increases in locomotor activity. Such effects of MK-801 were mediated through the ventral tegmental area and not the amygdala or n.accumbens. Neither MK- 801 nor L-NAME was able to prevent the expres-sion of cocaine-conditioned behaviors once established. DNQX (an AMPA receptor antagonist) was effective in this regard suggesting that while NMDA receptors participate in the formation of cocaine-condi-tioned behaviors, AMPA receptors are critically involved in the expression of such behaviors once established. More recently, we have found increases in C-fos expression in the piriform cortex, medial thalamus and amygdala by cocaine-associated cues indicating that these structures are involved in some aspects of cocaine- conditioned behaviors.